This research program is involved with studies of the response of blood vessel walls to injury. Under investigation by ultrastructural means are the functional properties and pathological responses of endothelium, basement membrane, subintimal constituents, and the smooth muscle cells of the intima and of the media. The normal modes of permeation of large molecules and their modification by catecholamines and kinins as well as other substances will be studied. The chemical structure and the role of the basement membrane in permeation and in repair of vessel injury are being examined. Differences between cells derived from intimal plaques and media from human beings are being examined by cell culture in vitro. Responses of cardiac muscle cells to injuries induced by catecholamines and their derivatives are being investigated. The mechanisms of release of biogenic amines from mast cells and platelets are being studied. All of these elements participate in the development of arteriosclerosis.